Scleroderma or systemic sclerosis (SSc) is frequently detected at an advanced stage due to diagnosis difficulties. Salivary biomarkers, if existing, could be used for predictive diagnosis of this disease. Human saliva contains a large number of proteins that can be used for diagnosis and are of great potential in clinical research. The use of proteomic analysis to characterize whole saliva (WS) in SSc has gained an increasing attention in the last years and the identification of salivary proteins specific for SSc could lead to early diagnosis or new therapeutic targets. This review will present an overview about the use of WS in SSc studies. The proteomic technologies currently used for global identification of salivary proteins in SSc, as well as the advantages and limitations for the use of WS as a diagnostic tool, will be presented.